Pertuzumab and everolimus (Afinitor) show promise for breast cancer treatment

Breast cancer is the leading cause of cancer deaths in women in the United States. On December 7, the results of the two studies were presented at the San Antonio Breast Cancer Symposium. An experimental drug from Genentech called pertuzumab kept breast cancer in remission for an average duration of 18 months when added to standard treatment, compared to 12 months for the standard treatment alone. It also strongly appears to be improving survival, and follow-up studies continue to support this trend. "You don't see that very often. ... It's a spectacular result," said one study author, Dr. Sandra Swain, medical director of Washington Hospital Center's cancer institute.

In a second study, a drug used for many years for organ transplantation patients but not tried against breast cancer, everolimus (Afinitor; Novartis AG), kept cancer at bay for an average duration of seven months in women whose breast cancer was worsening despite treatment with hormone-blocking drugs. A control group that received only hormonal medicine had only a three-month postponement in disease progression.

Afinitor works in a novel way, seems "unusually effective" and sets a new standard of care, noted Dr. Peter Ravdin, breast cancer chief at the UT Health Science Center in San Antonio. He has no relationship or financial interest with pharmaceutical manufacturers. Most breast cancer patients have tumors similar to those in the Afinitor study: their growth is fueled by estrogen.

The results of the studies were released a few weeks after Food and Drug Administration (FDA) approval was revoked for another Genentech drug, Avastin. The FDA claimed that did not meaningfully improve survival in breast cancer patients and that some women suffered fatal hemorrhages or other side effects; however, the drug will stay on the market for colon, lung, kidney and brain cancers. the drug is still marketed forhelp breast cancer patients. It still is sold for other tumor types.

Many breast cancer researchers regard the two new drugs to be some of the first major developments since Herceptin appeared on the market in 1998. That drug has become standard treatment for a certain type of breast cancer. "These are powerful advances ... an important step forward," noted Dr. Harold Burstein, a breast expert at Dana-Farber Cancer Institute in Boston who had no role in the studies.

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As with many new pharmaceuticals, the new drugs are likely to be very costly: up to $10,000 a month; furthermore, no current evidence exists that they are curative. The researchers suggest that the drugs might result in a cure when they are given to women with early-stage cancers when cure is possible, rather than the very advanced cases treated in these studies. Even of the drugs do not prove to be curative, approximately 40,000 women in the United States each year are stricken with cancer that spreads beyond the breast; thus, early treatment might significantly extend their survival.

On December 6, Genentech, a component of the Switzerland-based Roche Group, applied to the FDA for permission to sell pertuzumab as initial treatment for women like those in the study.

The drug targets cells that make an excessive amount of a protein called HER2; these cells are present in 20-25% of breast cancer cases. Herceptin attacks the same target; however in a different manner. As a result, the two drugs work synergistically (complement each other).

The pertuzumab study tested the combination with Herceptin in 808 women from Europe, North and South America, and Asia; it reported a six-month delay in any disease progression. All the women also received a chemotherapy drug, docetaxel. "That's a huge improvement" in such advanced cases, said study leader Dr. Jose Baselga, associate director of the Massachusetts General Hospital Cancer Center. Dr. Baselga is a paid consultant for Roche. To date, 165 deaths have occurred: 96 among the 406 women given Herceptin and chemotherapy alone, and only 69 among the 402 women also given pertuzumab. The researchers will be unable to determine actual survival improvement until more of the women expire from their disease. The most common side effects of the combination therapy were diarrhea, rash, and low white blood cell counts, which often occur with cancer treatment. However, this combination did not cause more heart problems, which is an issue with other Herceptin combinations.

Another study is testing pertuzumab in 3,800 women with early breast cancer. Genentech reports that it has not set a price for pertuzumab; however, Herceptin costs physicians $4,500 a month; the physicians usually mark up the price and add fees to infuse it. Herceptin's U.S. patent expires in 2019; thus, combination treatment should be more affordable once generic Herceptin is available.

The other study evaluated Afinitor, which has long been sold for preventing organ rejection after transplants and to treat a few less common cancers including the type of pancreatic cancer that Apple founder Steve Jobs succumbed to. It blocks one pathway cancer uses to spread. A one-month supply costs $11,000. The health of the 724 women in the study was deteriorating despite treatment with hormone-blocking medicines. They all were given Afinitor or another drug that they had not taken before. After about a year of follow-up, breast cancer progression was delayed seven months in the group getting Afinitor and three months in the control group.

What does FDA say about Afinitor for breast cancer treatment? Hope FDA acts quick on this, but carefully. So Afinitor does not become another quickly approved cancer treatment with disappointing and false results.

The FDA is somewhat of an enigma. For seriously ill cancer patients, they should relax the rule. The real hope for cancer victims is not for chemotherapeutic agents, which are in essence, poisons; rather, it lies with stimulating the immune system to destroy the caner cells, leaving the normal cells unharmed.

Thus, what Genentech announced about Pertuzumab for various types of cancers including brain, is only Phase III study. When do you think will become a mainstream treatment? How long does it take for drugs and FDA to gor from Phase III to full approved treatment? Thank you.

Timing varies. they pretty much do as they please. In general, they err on the side of caution. An example of fast-tracking was Avastin. After accelerating approval, the FDA recently banned it for breast cancer, citing minimal benefits and risk of serious side-effects. Despite the ban, however, physicians can still prescribe it at their discretion.

None of the treatments with chemotherapeutic drugs are miracle drugs. The only exception is methotrexate for choriocarcinoma. The real hope is in stimulating the immune system to destroy the cancer cells, leaving healthy cells unscathed.